Deciphering genetic bias underlying in global population for lipid homeostasis

Abstract

Lipid homeostasis refers to the balance of the levels of various lipids, such as fats and cholesterol, within cells and organisms. This balance is crucial for many physiological functions. Disruptions to lipid homeostasis, often caused by missense mutations in proteins involved in lipid metabolism, can lead to conditions like hyperlipidemia, increasing the risk of heart disease and other health problems. Currently, there is significant ongoing research aimed at deciphering the genetic basis of lipid homeostasis in different populations. This research could help develop personalized approaches to managing lipid levels, such as targeted medications or dietary interventions. To contribute to this area of research, we conducted a study focused on identifying common genetic variations associated with the regulation of lipid balance in different populations. Our study involved determining the prevalent mutational patterns and understanding their implications of nsSNPs at the protein structure. The study found unique amino acid exchange patterns among different ethnicities, with low-frequency substitutions more common in the RCT pathway. The African population had a distinct amino acid substitution frequency, and more inter-class conversions were observed when analyzed the impact of nsSNPs on chemical characteristics, indicates a significant impact on protein structure. In the Indian population, the majority of variants were found in the domain region. Structural analysis of 90 variants in 33 genes across six populations revealed that certain non-synonymous variants led to changes in protein secondary structure, caused destabilization, and impaired protein-protein interactions critical for proper lipid metabolism functioning. The study highlights the importance of investigating the effect of variants on protein structure to understand their implications in lipid-related diseases. The findings also suggest that the African and Indian populations may have undergone some genetic divergence leading to distinct amino acid substitutions.